The invention relates to substantive water-soluble 2-hydroxy sulfobetaines of cinnamidoalkylamines. More particularly, the invention relates to novel, cationic, non-hydrolysable, non-irritating UV-absorbing sulfobetaines of cinnamidoalkylamines which are substantive to fabric, skin and hair. The invention also relates to a process of manufacture of the said compounds and further to their use in hair, skin and fabric care formulations.
The harmful effects of solar UV-radiation on skin are well known. The UV-B (290-320 nm) portion of solar spectrum is largely responsible for erythema (sunburn) and cancer. [M. M. Rieger, Cosmet. Toiletries, 102 (3), 91, (1987); L. Taylor, Skin Cancer Foundation J., 4, (90) (1986)].
Similarly, photodegradative effect of UV-radiation on human hair is well documented. Continuous exposure to sunrays makes human hair color and makes human hair rough, brittle and difficult to comb. UV rays are reported to damage the proteins of cuticles. Prolonged irradiation results in diminished tensile strength due to breaking of disulphide bonds in keratin. [R. Beyak et al, J. Soc. Cosmet. Chem. 22, 667-668 (1971), E. Hoting et al, J. Soc. Cosmet. Chem. 46, 85-99 (1995)]
In addition, UV light is also known to fade coloured garments. [P. C. Screws, Text. Chem. Color, 11, 21 (1987); B. Milligan et al, Polym. Degrad. Stab. 10 (4), 335 (1985)]
A number of UV-absorbing compounds like derivatives of salicylic acid, benzophenones, benzotriazoles, cinnamic acid have been used in personal care products. However, all these molecules suffered from a major disadvantage of lack of substantivity. To make these UV-absorbing moieties more substantive, structural modification have been introduced.
U.S. Pat. No. 5,601,811 (1997) describes substantive UV-absorbing quaternary ammonium compounds containing cinnamidoalkylamine and product compositions for detergents, household cleaners and hair and skin personal care products. The synthesis of UV-absorbing sulphobetaines of the present invention employs sodium 3-chloro-2-hydroxy propane sulphonate to quaternize the cinnamidoalkylamines. High water solubility is desirable because these kind of substantive compounds can be formulated in oil-free compositions so that greasy feel of cosmetic preparations based on hydrophobic carrier can be avoided ! Due to their substantive nature constant reapplication of the sunscreen preparation is not necessary in activity like swimming. Hence, the compounds of the present invention are designed to address the need for highly water-soluble yet substantially substantive sunscreen molecules.
Thus the present invention provides novel, substantive, water-soluble 2-hydroxy sulfobetaines of cinnamidoalkylamines of Formula I, 
wherein, R1 is a substituent, selected from H, halo, xe2x80x94OH, xe2x80x94NH2, xe2x80x94NO2, xe2x80x94OCH3, xe2x80x94N(CH3)2, alkyl groups containing from 1 to 6 carbon atoms, alkoxy groups containing from 1 to 6 carbon atoms, alkylamino or N,N-dialkylamino groups containing from 1 to 6 carbon atoms;
R2 is selected from hydrogen, alkyl group containing from 1 to 12 carbon atoms;
R3 and R4 are independently selected from benzyl, alkyl group containing from 1 to 12 carbon atoms,
n is an integer from 1 to 6.
The invention further relates to a process of making a water-soluble 2-hydroxy sulfobetaines of cinnamidoalkylamines of Formula I 
wherein, R1 is a substituent, selected from H, halo, xe2x80x94OH, xe2x80x94NH2, xe2x80x94NO2, xe2x80x94OCH3, xe2x80x94N(CH3)2, alkyl groups containing from 1 to 6 carbon atoms, alkoxy groups containing from 1 to 6 carbon atoms, alkylamino or N,N-dialkylamino groups containing from 1 to 6 carbon atoms;
R2 is selected from hydrogen, alkyl group containing from 1 to 12 carbon atoms;
R3 and R4 are independently selected from benzyl, alkyl group containing from 1 to 12 carbon atoms,
n is an integer from 1 to 6;
wherein, a compound of Formula II is first reacted with a compound of Formula III and the intermediate of Formula IV thus obtained is quaternised with a compound of Formula V, 
wherein in all these Formulae, R1, R2, R3, R4 and n have the same meaning as Formula I and R5 of Formula II is selected form xe2x80x94OH, Clxe2x88x92 or xe2x80x94O(CH2)pCH3 with p=0 to 3.
In another aspect this invention provides compositions containing UV absorbing sulphobetaines that are water-soluble and substantive to skin, hair and textile fibres. The unique combination of substantivity to hair and skin, strong UV absorption and water-solubility of these 2-hydroxy sulfobetaines of cinnamidoalkylamines is very desirable for personal care products, especially for skin care applications.
The UV absorbing compounds of the present invention are sulfobetaines of cinnamidoalkylamines that are prepared by reacting lower alkyl ester of cinnamic acid or acid halides of cinnamic acid with an amino compound that is subsequently quaternised with sodium 3-chloro-2-hydroxy propane sulphonate.
In the process, the amidification reaction between a compound of the Formula II when R5xe2x95x90xe2x80x94OH or xe2x80x94O(CH2)pCH3 (p=0 to 3), with that of Formula III is carried out at from about 120xc2x0 C. to about 200xc2x0 C., under pressure from about 10 psi to about 100 psi, in the presence of a basic catalyst such as sodium methoxide, sodium hydroxide from 0.25% to 5.0% by weight of the reaction mass, to afford the intermediate compound of Formula IV. 
Preferred amount of such catalyst is 1.0% w/w of total reaction mass. The reaction is conveniently monitored by TLC or HPLC using UV detection. After the complete disappearance of cinnamic acid ester, the excess diamine is distilled off under vacuum.
Alternately, this reaction is carried out in the presence of a basic catalyst such as sodium methoxide, sodium hydroxide from 0.25% to 5.0% by weight of the reaction mass under atmospheric pressure, under blanket of nitrogen, with an arrangement for continuous selective removal of lower alcohol formed in the reaction.
Thus, the condensation reaction of one mole of cinnamic acid ester is carried with 1.0 to 3.0 moles of diamine at 120 to 200xc2x0 C., preferably at 180xc2x0 C., for 12 to 36 hours. The amines themselves can catalyse the reaction, however, the rates are found to be slower as compared with the bases like sodium methoxide and the like.
The same reaction can be performed using cinnamic acid in place of cinnamic acid ester at temperatures up to 200xc2x0 C. and pressures of 100 psi, keeping the same stoichiometry (1:1.0 to 3). The excess diamine serves as solvent for the reaction.
Cinnamic acid esters and amino compounds are selected that are liquid within the disclosed temperature and pressure range.
The amidification reaction between a compound of Formula II when R5xe2x95x90xe2x80x94Cl in the presence of a solvent, is carried out with that of Formula III at room temperature in the presence of solvent. The compounds of Formula IV are synthesised by reacting acid chlorides of Formula II (1.0 mole) when R5 is xe2x80x94Cl with the diamines of Formula III (1.0 to 1.2 mole) at 20-50xc2x0 C. in an inert solvent like dichloromethane, ethylene dichloride, tetrahydrofuran and the like.
In the process the cinnamidoalkylamines (Formula IV, 1 mole) are N-alkylated with sodium 3-chloro-2-hydroxy propane sulphonate quaternising agent (Formula V, 1.0 mole) in the presence of a suitable inert solvent that governs the temperature at which the reaction is carried out.
Quaternization of cinnamidoamines is carried out in solvents that include, water, lower alkanols, glycols and combinations thereof. Lower alkanols having one to four carbons atoms are suitable for use with the present 
invention. Glycols having from three to eight carbon atoms are suitable for use with the present invention. Mixtures of these solvents can also be used. Solvents used are from 20 to 80% by weight of the reaction mass. The cinnamidoalkylamines (Formula IV, 1 mole) are N-alkylated with quaternising agent (Formula V, 1.0 mole) in the presence of suitable solvents preferably water, isopropanol that govern temperatures at which the reaction is carried out.
The quaternisation reaction can be conveniently done in a pressure reactor as well as in an open system. The temperatures suitable for pressure reaction range from about 60-125xc2x0 C. with the pressures up to 50 psi. The pressures are governed by the amount of solvent and the temperature selected for the reaction. The conditions of reaction in an open vessel also get dictated by the choice of solvent. The reactions are usually carried out at boiling point or slightly below boiling point of the solvent employed. The resulting betaines are obtained as concentrated solutions. The progress of the reaction is monitored by measuring unquaternized amidoamine or by estimation of Clxe2x88x92.
The number and their nature of selected substituents should not be too hydrophobic to render the final sulfobetaines water-insoluble. For purposes of the present application, water-soluble compounds are defined as being soluble in water at levels above 15% w/w. These water-soluble compounds of this invention are useful for making compositions for skin and hair care and fabric care.
The preferred sulfobetaines in accordance with the present invention form aqueous solutions at levels of at least about 15% by weight. The more preferred sulfobetaines in accordance with the present invention have a solubility of at least about 25% by weight. The most preferred compounds have a water-solubility of at least 50% w/w.
The sulfobetaines in accordance with the present invention have the structure of Formula I.
As shown in Formula I, the benzene ring preferably contains one substituent at para position R1 is selected from moieties such as halo, p-OH, xe2x80x94NH2, xe2x80x94NO2, xe2x80x94OCH3, xe2x80x94N(CH3)2.
Referring again to Formula I, the amido nitrogen is preferably is either unsubstituted (R2 is hydrogen) or may contain a substituent, selected from alkyl groups containing up to 12 carbon atoms. The quaternized nitrogen of the compounds in accordance with the present invention preferably contains two substituents, R3 and R4, as depicted in Formula I, R3 and R4 are independently selected from hydrogen, benzyl and alkyl groups containing up to 6 carbon atoms.
The compounds of the present invention are sulfobetaines of cinnamidoalkylamines as shown in Formula I, in which n is an integer between 1 and 6, both inclusive. Preferred compounds in accordance with the present invention are sulfobetaines of cinnamidoalkylamines in which n is an integer between 2 and 6, both inclusive and most preferably, n of Formula I is 3.
In another embodiment the process of the present invention relates to manufacture of a compound of Formula I, namely, 3-(N-p-methoxy cinnamidopropyl, N,N-dimethyl ammonium)-2-hydroxy propane-1-sulphonate, when R1xe2x95x90xe2x80x94OCH3, R2xe2x95x90H, R3xe2x95x90R4xe2x95x90xe2x80x94CH3, and n=3, from the compounds of Formula II, namely, p-methoxy ethyl cinnamate), and Formula III, namely, N,N-dimethylpropyldiamine, to form an intermediate compound of Formula IV, namely, p-methoxy cinnamidopropyldimethyl amine and Formula V, namely, sodium 3-chloro-2-hydroxy propane sulphonate, with respective substituents R1 of Formula II, R2, R3, R4 and n of Formula III as defined for the compounds of Formula I in this embodiment, and R5 of Formula II being ethoxy.
Cinnamidoalkylamine (Formula IV) are in turn synthesized by amidification of lower alkyl esters of cinnamic acid (Formula II, alkoxy group (R5) may vary from C1 to C4) by appropriate diamines (Formula III) containing a tertiary amino group.
R1, R2, R3 and R4 of cinnamidoalkylamine (Formula IV) and the diamine (Formula III) are the same as described with respect to Formula I.
The amidification reaction is performed at temperatures up to 200xc2x0 C. and pressures up to 100 psi. Accordingly, cinnamic acid esters and amino compounds are selected that are liquid within the disclosed temperature and pressure range. This reaction generates lower alcohol that need not be distilled out.
In the present invention the reaction of one mole of cinnamic acid ester is carried with 1.2 to 3 moles of diamine at 130 to 200xc2x0 C., preferably at 180xc2x0 C., for 12 to 36 hours. This condensation is catalysed by bases like sodium hydroxide, sodium methoxide or ethoxide, potassium hydroxide and the like. The amines themselves can catalyse the reaction, however, the rates are found to be slower as compared with the bases like sodium methoxide and the like.
From about 0.5% to 5.0% w/w of the basic catalyst should be employed. Preferred amount of such catalyst is 1.0% w/w. The reaction is conveniently monitored by TLC or HPLC using UV detection. After the complete disappearance of cinnamic acid ester the excess diamine is distilled off under vacuum.
This amidification can also be carried out under atmospheric pressure under blanket of nitrogen with an arrangement for selective condensation of the diamine and continuous removal of lower alcohol. The same reaction can be performed using cinnamic acid in place of cinnamic acid ester at temperatures up to 200xc2x0 C. and pressures of 100 psi, keeping the same stoichiometry (1:1.2 to 3). The excess diamine serves as solvent for the reaction.
The sulfobetaines (Formula I) of the present invention are synthesized as concentrated solutions by N-alkylating cinnamidoamines (Formula IV) with sodium 3-chloro-2-hydroxy propane sulphonate having Formula V.
In another aspect this invention provides compositions containing quaternary ammonium compounds that are water-soluble, UV-absorbing and substantive to skin, hair and textile fibres. The hair care and skin care compositions containing compounds of Formula I can be solutions, dispersions or emulsions. The quaternary compounds of Formula I are soluble in water, alcohols, glycols, mixtures thereof, mixtures of alcohols and water and mixtures of glycols and water.
Lotions may be formed using compounds of Formula I, with or without one or more of the inert solvents like ethyl alcohol, isopropyl alcohol or propylene glycol, by combining with film forming polymers like proteins, polyvinyl pyrrolidone, polyvinyl alcohols and the like, film-forming starches and resins and the like.
Oil-in-water and water-in-oil emulsion can also be employed as vehicles to form lotions and creams. Conventional oil soluble UV-absorbing compounds like cinnamates, salicylates, p-aminobenzoates, benzophenones can be dissolved in oily phase of emulsion/lotions. The water-soluble sunscreens of the present invention are dissolved in an aqueous phase of the emulsion and combined with the oily phase using a suitable cationic emulsifier such as stearylkonium chloride.
Vegetable or mineral oils suitable for use as oil phase include mineral oil, petroleum, castor oil, sesame oil and the like. The quaternary ammonium compounds of the present invention are added to aqueous phase which is then subsequently emulsified with oily phase using an emulsifier like stearylkonium chloride or non-ionic emulsifiers like polysorbate-80, fatty alcohol ethoxylates and the like.
Perfumes, fragrances, anti-oxidants, preservatives, dyes colorants, insect repellents, fillers and suspended particulate matter, emollients, humectants, thickeners and the like may optionally be included in the sunscreen and tanning compositions of the present invention.
The sunscreen and tanning compositions of the present invention contain an effective amount of compounds of Formula I to prevent erythema. In general, an amount of about 0.5% to 10% w/w of the total composition is used. Face powder compositions of the present invention contain compounds of Formula I in an effective amount of 0.1% w/w to 0.5% w/w.
The compositions containing compounds of Formula I may contain one or more of the other cosmetic ingredients like surfactants, other sunscreen chemicals, after sun treatment materials, emollients, humectants, perfumes, anti-perspirants, moisturisers, color cosmetic materials, herbal extracts, occlusive oils and essential oils.
The compositions of compound with Formula I provide hair protection from UV radiation in addition to good conditioning effect. The hair protecting preparations can be formulated in the form of creams, lotions, tonics or gels. The compounds of the present invention may also be formulated as hair care product such as shampoos, cream rinses, hair conditioners, hair dressing preparations, hair relaxers, hair coloring products and the like, capable of protecting hair from UV-B radiation.
The rinse-off preparations like shampoos, face washes and bathing bars contain 0.5 to 8.0% w/w of compounds of Formula I. It may be noted that these betaines are compatible with usual anti-dandruff, anti-microbial agents like Zinc pyrithione, Irgasan, Pyroctone. Hence, these compounds of Formula I can be incorporated in anti-dandruff shampoos.
The compounds of Formula I are completely compatible with anionic surfactants like sodium lauryl ether sulphate due to its zwittwerionic nature. The transparent shampoo formulation based on sodium lauryl ether sulphate has been shown to deposit the UV-absorbing betaine compounds on hair (Example III).
The cream hair conditioner is an example of emulsion type with both water-soluble and water-insoluble sunscreens is given in Example IV.
Soap bars, both opaque and transparent/translucent can be formulated with compounds of UV-absorbing compounds of Formula I. In soap bars, the sulfobetaines of cinnamidoalkylamines can be incorporated from 0.5 to 10.0% w/w, more preferably from 1.0 to 2.0% w/w of total composition. It may be noted that the compounds of Formula I in the following combi-bar formulation are compatible with anionic surfactants (Example V).
For everyday use a sunscreen cream to protect the skin from both UV-A and UV-B radiation can be formulated as given in Example VI. The substantive UV absorbers, both water-insoluble and water-soluble (compounds of Formula I) can be conveniently incorporated at 2.0% each w/w of total composition. To cover UV-A range butyl methoxy dibenzoyl methane (Parsol 1789) is incorporated.
Furthermore, the compounds of Formula I of the present invention can be effectively incorporated into typical detergent powder and household cleaning product compositions to impart anti-fading effect to colored fabric through substantivity. Typical detergent and household cleaning product compositions in accordance with the present invention include one or more surfactants, selected from anionic, cationic, nonionic and amphoteric detergents, alone or in combination. A typical detergent powder has been shown to deposit zwitter ionic photofilters of the present invention on fabric (Example VII).
The hair and skin protecting and detergent and household cleaning compositions of the present invention are also formed by admixing, dissolving the compounds of Formula I into the desired cosmetically acceptable diluent and carrier. The preferred cosmetic compositions are solutions, dispersions or emulsions. The compositions contain an effective amount of one or more of UV-absorbing and conditioning compounds of the present invention to prevent erythema and darkening of skin due to solar damage.
In general, an amount of about 0.5% to about 10% w/w and preferably between 2.5 to 8.0% w/w of total cosmetic composition of compounds of Formula I are useful in personal hair and skin care products, sunscreens and tanning lotions. Typically, the ingredients are combined with mixing and heating if necessary until a uniform, homogeneous product is formed. With respect to the emulsion products of the present invention, the water-soluble and water-insoluble ingredients are mixed together separately and combined with suitable emulsifier, preferably a cationic emulsifier, to form an emulsion.
Finally, the substantive UV-B absorbers of the present invention are non-hydrolysable and contain the most widely used chromophore of cinnamido moiety for UV absorption. A representative substantive sulfobetaines of cinnamidoalkylamines of the present invention, 3-(N-p-methoxy cinnamidopropyl, N,N-dimethyl ammonium)-2-hydroxy propane-1-sulphonate, has molar extinction coefficient, ∈ of 24,000. It is non-irritant and non-mutagenic (Ames test). High water-solubility coupled with substantivity of the compounds of the present invention, is very much desired in cosmetic formulations without an oily phase.